Implantable intraventricular sampling and infusion access device

ABSTRACT

In some embodiments, a device may include an intraventricular access device and an infusion device. The intraventricular access device may include more than one catheter and a container. In some embodiments, the catheter may include an aspiration lumen and an infusion lumen. A distal end of the intraventricular portion of the catheter may be positionable, during use, in a subject&#39;s brain fluid. In some embodiments, the container may be coupled to a proximal end of the aspiration lumen. The proximal end of the aspiration lumen may be in fluid communication with the container. The proximal end of the infusion lumen may be in communication with an infusion pump. In some embodiments, the device inhibits cross contamination between a first fluid in the aspiration lumen and a second fluid in the infusion lumen. In some embodiments, the container may include a barrier positioned between a proximal opening of the aspiration lumen and at least a portion of the infusion lumen adjacent to and/or associated with the container. The barrier may inhibit penetration of a surgical instrument.

PRIORITY CLAIM

This application claims priority to U.S. Provisional Application Ser.No. 62/367,713 entitled “IMPLANTABLE INTRAVENTRICULAR SAMPLING ANDINFUSION ACCESS DEVICE” filed on Jul. 28, 2016, which is incorporatedherein by reference in its entirety.

BACKGROUND OF THE INVENTION 1. Field of the Invention

The present disclosure generally relates to intraventricularadministration of drugs to the brain. More particularly, the disclosuregenerally relates to an intraventricular access device configurable toprovide continuous drug infusion and/or access for sampling ofcerebrospinal fluid.

2. Description of the Relevant Art

One of the principle reasons for directly administering drug therapiesto the brain is due to the blood-brain barrier (BBB). The BBB limitsthat passage of nearly all large molecule and the majority of smallmolecule drugs (<500 Da) to the brain parenchyma. Since the BBB limitsthe penetration of drugs from the vasculature to the brain tissue, mostdrugs that are administered orally or by intravenous infusion do notreach sufficient concentrations in the brain parenchyma to havetherapeutic effects. In addition, drugs that may have the highestpotential efficacy against cancerous tissue are unable to reach thetarget tissue. For example, trastuzumab, a humanized IgG1 kappamonoclonal antibody for the treatment of metastatic breast cancer has acerebrospinal fluid (CSF) level that is 300-fold lower than plasmalevels when administered intravenously.

Several methods have been proposed to bypass the BBB to increase drugconcentrations in the brain. These include methods for altering theadministration of drugs for brain delivery including:convection-enhanced delivery (CED), intra-arterial injection, high dosesystemic chemotherapy, drug-loaded wafers that are inserted directlyinto the tumor resection cavity, and administration of drugs to the CSF.

Methods also exist to temporarily increase the permeability of the BBBand include the use of osmotic solutions (mannitol), pulsed ultrasoundin combination with microbubbles, and radiation therapy.

One method for direct administration of drugs to bypass the BBB is theuse of an ommaya reservoir, which is described below. The OmmayaReservoir is a type of device that allows for direct access to the CSFfrom a syringe or external pump without additional surgery at each drugadministration. An external ventricular drain is another type of devicethat allows for access to the CSF, typically to drain excess CSF torelieve and reduce intracranial pressure (ICP).

The Ommaya Reservoir is an intraventricular catheter system that allowsfor either sampling of cerebrospinal fluid or less commonly intermittentdirect administration of drugs to the CSF. They were invented in 1963and when used for chemotherapy are primarily used for the delivery ofchemotherapy agents such as methotrexate or Ara-C to the CSF forpatients with leptomeningeal disease and for continuous sampling of theCSF for potential infection, progression of CSF based cancers andoccasionally for obtaining a drug level. One example of such a reservoiris the Integra™ Reservoir (Integra LifeSciences Corporation).

Several types of external ventricular drains exist to provide access tothe CSF. These types of catheters are classified as Class 2 medicaldevices by the FDA. They may have an antibacterial coating to limitinfection, which can occur in up to 25% of catheter placements in thebrain. For example, the Ares™ Antibiotic Impregnated Catheter(Medtronic) and Bactiseal® (Codman Neuro, DePuySynthes, Johnson &Johnson) are impregnated with rifampicin and clindamycin and preventbacterial colonization on all surfaces for up to 28 days. Otherantibiotics such as minocycline/rifampin or silver may also be used tocoat the device to limit infection. They may also contain bariumimpregnation for visualization on X-ray to verify proper positioning ofthe device within the brain.

Drug Infusion into the lumbar spine CSF via implantable catheters exist.These catheters infuse drug into a small space with small flow volumeswhich is because the space required for infusion is small. The size ofthe holes tends to be small.

In terms of brain catheters currently used for drainage, an example isthe Ares™ (Medtronic) ventricular catheter has 32 flow holes with fourlines of 8 holes spaced at 90° intervals—to limit clogging fromventricular contents though never a focus on brain drug delivery. Thesedevices are never used for chronic brain drug delivery.

Catheters designed for convection enhanced delivery (CED) have beendeveloped. CED catheters are designed to infuse drug directly into thetargeted tissue. The barium-impregnated Medtronic® PS Medical (Goleta,Calif., USA; Catalog number 43209) and Vygon US LLC (Valley Forge, Pa.,USA) are examples of devices that have been used in CED trials (Debinskiand Tatter 2009). Infuseon Therapeutics (U.S. Pat. Nos. 8,808,234 and8,979,822 which are incorporated by reference herein) is also developinga new catheter design for CED that allows for delivery of drugs to thebrain via four independent flexible micro catheters. The device isdesigned for use over up to several days (but not for chronic use overweeks or months). The catheters are made from silicon and eachmicrocatheter has a diameter of 0.38 mm. The main issue with CEDcatheters is backflow of the infusate during infusion and the lack ofability to use them for chronic infusion.

There are known complications beyond intracranial hemorrhage of braindrains which are external to the body and placed most commonly in casesof brain trauma, subarachnoid hemorrhage or post neurosurgical.Infection is one of the most common types of complications associatedwith such devices. A common practice aimed at reducing this is toadminister intravenous antibiotics to cover common skin flora for theduration of EVD placement. Though this appears to carry some benefit, itmay contribute to the development of resistant organisms.Antibiotic-impregnated and ionized silver particle coated EVD cathetersoffer a similar level of protection compared with prophylacticintravenous antibiotics but come at a cost. Other strategies includesampling an EVD only when infection is suspected, monitoring EVDdressing site for drainage suggestive of CSF leak, maintainingcollection system in the upright position, and not routinely changingdrain tubing. In the setting of infection, it is common consensus thatthe colonized EVD catheter be removed and replaced with a new catheter,preferentially at a new site. Minimizing infection is a requirement forlonger term placement.

The present invention relates to the direct administration of drugtherapies to the brain through an intraventricular access device thatallows for access to the CSF through a port located just beneath thescalp of a patient. The system can furthermore be attached to animplantable drug pump (e.g. Prometra® Programmable Pump by FlowonixMedical or the Synchromed® by Medtronic) or an external syringe orequivalent type pump.

Accordingly, there is a desire to provide a device for the directadministration of drug therapies to the brain through anintraventricular access device that allows for access to the CSF througha port located just beneath the scalp of a patient.

SUMMARY

In some embodiments, a device may include an intraventricular accessdevice. The intraventricular access device may include a catheter and acontainer. In some embodiments, the catheter may include an aspirationlumen and an infusion lumen. A distal end of the catheter may bepositionable, during use, in a subject's brain. In some embodiments, thecontainer may be coupled to a proximal end of the aspiration lumen. Theproximal end of the aspiration lumen may be in fluid communication withthe container. In some embodiments, the device inhibits crosscontamination between a first fluid in the aspiration lumen and a secondfluid in the infusion lumen. In some embodiments, the container mayinclude a barrier positioned between a proximal opening of theaspiration lumen and at least a portion of the infusion lumen adjacentto and/or associated with the container. The barrier may inhibitpenetration of a surgical instrument. The container may include a markerto indicate a position of the barrier.

In some embodiments, at least a portion of the infusion lumen ispositioned in the aspiration lumen or at least a portion of theaspiration lumen is positioned in the infusion lumen. In someembodiments, the aspiration lumen and the infusion lumen may include twodifferent lumens positioned adjacent one another.

In some embodiments, the aspiration lumen and the infusion lumen aredifferent lengths when positioned, during use, in the subject's brainsuch that a distal end of the aspiration lumen and a distal end of theinfusion lumen are positioned a distance away from one another.

In some embodiments, a distal end of the aspiration lumen comprises afirst opening and a distal end of the infusion lumen comprises a secondopening. The first opening and the second opening may be directed in asubstantially opposing directions to inhibit cross contamination offluids.

In some embodiments, a distal end of the aspiration lumen and/or theinfusion lumen comprises at least one opening or a plurality of openingswhich are inhibited from opening except when pressure is applied to theopening.

In some embodiments, at least a portion of the container is formed frommaterial that is penetrable by a needle (e.g., a hypodermic needle) andsubstantially reseals after extraction of the needle.

In some embodiments, at least portions of the device are formed fromand/or coated in biocompatible materials which inhibit cell adhesionand/or comprises an antimicrobial.

In some embodiments, the infusion lumen may be coupled to a pumppositioned externally or internally relative to the subject.

In some embodiments, a method includes aspirating and infusing at leasta portion of a subject's brain. The method may include penetrating anupper portion of a container of a device using a needle. The method mayinclude aspirating a first fluid from a first portion of a subject'sbrain through an aspiration lumen coupled to the container and using theneedle. The method may include infusing a second fluid into a secondportion of a subject's brain through an infusion lumen coupled to thecontainer and the aspiration lumen. The method may include inhibitingpenetration of the infusion lumen by the needle.

In some embodiments, the method may include infusing the second fluidusing a pump coupled to the infusion lumen, wherein the pump ispositioned externally or internally relative to the subject. The methodmay include positioning at least a portion of the infusion lumen coupledto a pump subcutaneously.

In some embodiments, the method may include positioning at least aportion of the aspiration and/or the infusion lumen in the subject'sbrain using a substantially inflexible stylet. The stylet may bepositioned in the aspiration lumen by running the stylet through thecontainer. The method may include observing at least a portion of thedevice during implantation using neuroimaging.

In some embodiments, the method may include inhibiting penetration ofthe infusion lumen by the needle using a barrier positioned between aproximal opening of the aspiration lumen and at least a portion of theinfusion lumen adjacent to and/or associated with the container.

In some embodiments, the method may include inhibiting at least oneopening at a distal end of the aspiration lumen and/or the infusionlumen from opening except when pressure is applied to the opening in afirst direction. The method may include inhibiting the at least oneopening in a second direction from opening even under pressure.

BRIEF DESCRIPTION OF THE DRAWINGS

Advantages of the present invention may become apparent to those skilledin the art with the benefit of the following detailed description of thepreferred embodiments and upon reference to the accompanying drawings.

FIG. 1 depicts a diagram of a cross sectional view of an embodiment of aportion of an intraventricular access device, specifically a catheterdesign with a concentric dual lumen design. Infusion and sampling portsare implanted in one of the lateral ventricles. The infusion port (outerlumen) is connected to an implanted pump.

FIG. 2 depicts a diagram of a cross sectional view of an embodiment of aportion of an intraventricular access device, specifically a side byside dual lumen design including an infusion pathway distinct from theinfusion catheter coming from the pump which is shielded from thesampling port from being penetrated by a or other needle duringaspiration.

FIG. 3 depicts a diagram of a cross sectional view of an embodiment ofan intraventricular access device implanted with the sampling andinfusion ports located in one of the lateral ventricles. The infusionand sampling catheter in the brain is connected to a container which isin turn connected to an implantable pump that is located in the abdomen.

FIG. 4 depicts a diagram of a cross sectional view of an embodiment ofan intraventricular access device implanted with the sampling andinfusion ports located in one of the lateral ventricles. The infusionand sampling catheter in the brain is connected to a container which isin turn connected to an external syringe pump.

FIG. 5 depicts a diagram of a cross sectional view of an embodiment of aportion of an intraventricular access device, specifically a side byside dual lumen design. The infusion and sampling ports are implanted inone of the lateral ventricles. A container fluidly coupled to at leastthe infusion lumen may allow either directly inject drugs into theventricles, or to sample CSF from the patient using an external syringe(or an external pump).

FIG. 6 depicts a diagram of a cross sectional view of an embodiment ofan access device implanted with the sampling and infusion ports locatedover the cisterna magna and the cerebellum. The tip of the catheter canbe directed to the cisterna magna, cisterns in the cerebellopontineangle, in the fourth ventricle or in the supra-cerebellar cisterndirection. The infusion and sampling catheter in the brain is connectedto a container which is in turn connected to an implantable pump that islocated in the abdomen.

FIG. 7 depicts a diagram of a cross sectional view of an embodiment of aportion of an intraventricular access device, specifically a side byside dual lumen design. The infusion and sampling ports are implanted inone of the lateral ventricles. The infusion port (right lumen inillustrator) is connected to an implanted pump located near the abdomen.

FIGS. 8A-F depict diagrams of a cross sectional view of severalembodiments of a various dual lumen catheters that may be used for thedevice described herein as well as one or more stylets positioned in oneor more of the lumens.

FIG. 9 depicts a diagram of a cross sectional view of an embodiment of aportion of an intraventricular access device, specifically a side byside dual lumen design with multiple flow holes in the infusioncatheter. The flow holes may be open or may each consist of small“slits” that open when drug is infused (when there is positive pressure)and close when drug is not infused.

FIG. 10 depicts a diagram of a top view of an embodiment of a portion ofan implanted intraventricular access device detailing an implantationmethod.

FIG. 11 depicts a diagram of a side view of an embodiment of a portionof an implanted intraventricular access device detailing an implantationmethod.

FIG. 12 depicts a diagram of a cross sectional view of an embodiment ofa portion of an implanted intraventricular access device detailing animplantation method.

While the invention is susceptible to various modifications andalternative forms, specific embodiments thereof are shown by way ofexample in the drawings and may herein be described in detail. Thedrawings may not be to scale. It should be understood, however, that thedrawings and detailed description thereto are not intended to limit theinvention to the particular form disclosed, but on the contrary, theintention is to cover all modifications, equivalents and alternativesfalling within the spirit and scope of the present invention as definedby the appended claims.

The headings used herein are for organizational purposes only and arenot meant to be used to limit the scope of the description. As usedthroughout this application, the word “may” is used in a permissivesense (i.e., meaning having the potential to), rather than the mandatorysense (i.e., meaning must). The words “include,” “including,” and“includes” indicate open-ended relationships and therefore meanincluding, but not limited to. Similarly, the words “have,” “having,”and “has” also indicated open-ended relationships, and thus mean having,but not limited to. The terms “first,” “second,” “third,” and so forthas used herein are used as labels for nouns that they precede, and donot imply any type of ordering (e.g., spatial, temporal, logical, etc.)unless such an ordering is otherwise explicitly indicated. For example,a “third die electrically connected to the module substrate” does notpreclude scenarios in which a “fourth die electrically connected to themodule substrate” is connected prior to the third die, unless otherwisespecified. Similarly, a “second” feature does not require that a “first”feature be implemented prior to the “second” feature, unless otherwisespecified.

Various components may be described as “configured to” perform a task ortasks. In such contexts, “configured to” is a broad recitation generallymeaning “having structure that” performs the task or tasks duringoperation. As such, the component can be configured to perform the taskeven when the component is not currently performing that task (e.g., aset of electrical conductors may be configured to electrically connect amodule to another module, even when the two modules are not connected).In some contexts, “configured to” may be a broad recitation of structuregenerally meaning “having circuitry that” performs the task or tasksduring operation. As such, the component can be configured to performthe task even when the component is not currently on. In general, thecircuitry that forms the structure corresponding to “configured to” mayinclude hardware circuits.

Various components may be described as performing a task or tasks, forconvenience in the description. Such descriptions should be interpretedas including the phrase “configured to.” Reciting a component that isconfigured to perform one or more tasks is expressly intended not toinvoke 35 U.S.C. § 112 paragraph (f), interpretation for that component.

The scope of the present disclosure includes any feature or combinationof features disclosed herein (either explicitly or implicitly), or anygeneralization thereof, whether or not it mitigates any or all of theproblems addressed herein. Accordingly, new claims may be formulatedduring prosecution of this application (or an application claimingpriority thereto) to any such combination of features. In particular,with reference to the appended claims, features from dependent claimsmay be combined with those of the independent claims and features fromrespective independent claims may be combined in any appropriate mannerand not merely in the specific combinations enumerated in the appendedclaims.

It is to be understood the present invention is not limited toparticular devices or biological systems, which may, of course, vary. Itis also to be understood that the terminology used herein is for thepurpose of describing particular embodiments only, and is not intendedto be limiting. As used in this specification and the appended claims,the singular forms “a”, “an”, and “the” include singular and pluralreferents unless the content clearly dictates otherwise. Thus, forexample, reference to “a linker” includes one or more linkers.

DETAILED DESCRIPTION Definitions

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art.

The term “catheter” as used herein generally refers to medical devicesthat can be inserted in the body to treat diseases or perform a surgicalprocedure.

The term “connected” as used herein generally refers to pieces which maybe joined or linked together.

The term “coupled” as used herein generally refers to pieces which maybe used operatively with each other, or joined or linked together, withor without one or more intervening members.

The term “directly” as used herein generally refers to one structure inphysical contact with another structure, or, when used in reference to aprocedure, means that one process effects another process or structurewithout the involvement of an intermediate step or component.

The term “stylet” as used herein generally refers to a probe, typicallya slender probe.

Intraventricular Access Device:

CSF sampling is inherently important both from a safety and efficacyperspective.

From a safety perspective, the ability to both monitor potentialinfection as well as drug levels is important. From an efficacyperspective, understanding drug levels will be increasingly important tomonitor drug treatments. Accordingly, there is a desire to provide adevice for the direct administration of drug therapies to the brainthrough an intraventricular access device that allows for access to theCSF through a port located just beneath the scalp of a patient. Thesystem can furthermore be attached to an implantable drug pump or anexternal syringe or equivalent type pump.

In some embodiments, an intraventricular access device may provide animplantable drug delivery device that facilitates drug administration aswell as sampling in the brain of a human patient. The access for drugsampling may occur at a separate location than the drug infusion tominimize cross contamination. Drug sampling may be performed with asharp needle and as such the intraventricular access device includesprotections such that the needle for sampling will not penetrate theinfusion catheter. With such design safeguards, mixing and inaccuraciesmay be avoided. Both infusion and sampling access points within thebrain are done relatively close to each other as such sampling andinfusion may be accomplished in such a way to minimize crosscontamination. The drug delivery device is adapted for implantation intoa human subject and drug delivery to the CSF. The drug delivery deviceincludes a support structure that may be accessed via skin puncture tosample the CSF.

In some embodiments, a device may include an intraventricular accessdevice 100. FIG. 1 depicts a diagram of a cross sectional view of anembodiment of a portion of an intraventricular access device 100,specifically a catheter design with a concentric dual lumen design.Infusion and sampling ports are implanted in one of the lateralventricles 200 of a subject's brain 300. The infusion port (outer lumen)is connected to an implanted pump. The intraventricular access devicemay include a catheter 110 and a container 120. In some embodiments, thecatheter may include an aspiration lumen 110 a and an infusion lumen 110b. A distal end of the catheter (e.g., 5-6 cm length) may bepositionable, during use, in a subject's brain. In some embodiments, thecontainer 120 may be coupled to a proximal end of the aspiration lumen110 a. The proximal end of the aspiration lumen may be in fluidcommunication with the container. In some embodiments, the deviceinhibits cross contamination between a first fluid in the aspirationlumen and a second fluid in the infusion lumen. Cross contamination maybe inhibited by using two separate lumens for sampling and infusion.

Cross contamination may be inhibited using other systems and/or methods.In some embodiments, the container 120 may include a barrier 130positioned between a proximal opening of the aspiration lumen and atleast a portion of the infusion lumen adjacent to and/or associated withthe container. The barrier may inhibit penetration of a surgicalinstrument (e.g., hypodermic needle). For example, a needle may be usedto collect a sample from the container conveyed up through theaspiration lumen and the barrier may inhibit accidental puncture of theinfusion lumen by the needle during the procedure. FIG. 2 depicts adiagram of a cross sectional view of an embodiment of a portion of anintraventricular access device 100, specifically a side by side duallumen design including an infusion pathway distinct from the infusioncatheter coming from the pump which is shielded from the sampling portfrom being penetrated by a hypodermic or other needle during aspiration.

In some embodiments, the infusion side or segment and the infusionpathway will be covered by a barrier (e.g., metal or other hard plasticmaterial (e.g. PEEK)) to limit the ability of a needle to penetrate andpotentially cause a fenestration between the two sides. The top portionon the container may be a silicon-type material that can be punctured bya needle, but which re-seals after the needle is withdrawn. In someembodiments, the container may have guide members 180 (e.g., be acone-shape) so that the needle will be guided to the location of thesampling lumen 110 a.

In some embodiments, the container may include a marker to indicate aposition of the barrier. In some embodiments, one or more portions ofthe intraventricular access device 100 may include a marker of some kindincluding, but not limited to, any portion of the device positionablewithin the subject. The device may include multiple individuallydistinguishable markers. Markers may be used to assess a position of oneor more portions of the device during and/or after implantation in asubject. A portion of the implant may include none, one or multiplemarkers. Markers may provide radiographic opacity. Markers may bebiocompatible. Markers may be of any size or shape. In some embodiments,a system may have multiple markers with different shapes in order tomore easily identify different portions of the system and/or anorientation of one or more portions of the device. In some embodiments,one or more markers may be formed from gold or tantalum.

The intraventricular access device may be designed to operate as part ofa drug delivery system. The system includes a catheter that has distalopenings in the CSF. The proximal side of the catheter is connected to amodified reservoir or container that may be accessed using, for example,a standard needle to draw CSF fluid from the distal end of the catheterto sample the CSF. In some embodiments, the infusion lumen may becoupled to a pump positioned externally or internally relative to thesubject. For example, the container may contain a pathway for druginfusion and is connectable to a catheter which may connect to animplantable, programmable, refillable, drug pump. The pump may beimplanted in the abdominal region of a patient. FIG. 3 depicts a diagramof a cross sectional view of an embodiment of an intraventricular accessdevice 100 implanted with the sampling and infusion ports 110 a-blocated in one of the lateral ventricles 200. The infusion and samplingcatheter in the brain is connected to a container 120 which is in turnconnected to an implantable pump 140 (e.g., via an extension of theinfusion lumen or an additional lumen 110 c coupled to the infusionlumen) that is located, for example, in the abdomen. In someembodiments, a drug pump may be connected to an external pump 150 inaddition to or in the alternative to an implantable pump. FIG. 4 depictsa diagram of a cross sectional view of an embodiment of anintraventricular access device 100 implanted with the sampling andinfusion ports 110 a-b located in one of the lateral ventricles 200. Theinfusion and sampling catheter in the brain is connected to a container120 which is in turn connected to an external pump 150 (e.g., a syringepump via an extension of the infusion lumen or an additional lumen 110 ccoupled to the infusion lumen).

In some embodiments, implantable drug pumps such as the Synchromed®(Medtronic) or Prometra® (Flowonix) may be used for local and continuousinfusion of drug therapies. These drug pumps are currently indicated forintrathecal drug delivery and have 20-40 mL refillable reservoirs. Theyare indicated for the treatment of chronic, intractable pain, severespasticity, and cancer. Alternatively, an external syringe type pump canbe utilized. Syringe type pumps can include a pump like a Baxter 150XL.For other descriptions of potential pumps

Medications which may be introduced using the herein described systemare not limited. In some embodiments, Morphine and Baclofen are bothdrugs that could be used as well as chemotherapies and other drugs fortreatment of chronic and nonchronic diseases of the brain.

In some embodiments, aspiration lumen 110 a may function as a samplingportal for obtaining a sample of a subject's fluid. FIG. 5 depicts adiagram of a cross sectional view of an embodiment of a portion of anintraventricular access device 100, specifically a side by side duallumen design. The infusion and sampling ports are implanted in one ofthe lateral ventricles. A container 120 fluidly coupled to at least theinfusion lumen 110 a may allow either directly inject drugs into theventricles, or to sample CSF from the patient using an external syringe160 (or an external pump 150).

In some embodiments, in the access device 100 the lumens 110 aretunneled up to the cisterna magna along the spine. FIG. 6 depicts adiagram of a cross sectional view of an embodiment of an access device100 implanted with the sampling and infusion ports located in thecisterna magna. The infusion and sampling catheter in the brain isconnected to a container 120 which is in turn connected to animplantable pump 140 that is located in the abdomen. The lumens 110inserted into a spinal canal and tunneled (e.g., using a guidewire). Insome embodiments, the container 120 (e.g., sampling reservoir) wouldeither sit above the occipital bone, or the muscle layer of the lumbarspine or adjacent to the pump (e.g., in the abdomen or over the back).As described herein with other embodiments the device 100 may becoupled, during use, to an internal or an external pump. In the currentembodiment, features described herein to prevent cross contamination(e.g., a barrier) may be utilized. In the current embodiment, featuresdescribed herein may be utilized including wherein the ends of thelumens being separated by a distance (e.g., 5 mm to 1 cm). The container(e.g., sampling reservoir) may separate from the double lumens so thatthe lumens are joined but the container has been separated from thejoint lumens. For example, a T-shaped separation may be used in thetubing with one pathway from the T moving towards an aspirationreservoir and one pathway towards the infusion system. A T coupling 115may be used in other embodiments disclosed herein. An installationstylet as described herein may be temporarily positioned in the infusionlumen or the aspiration lumen during placement in a subject. The devicemay be positioned using neuroimaging or other forms of intraoperativedetection. Markers (e.g., metal portions of the device) may be used forneuroimaging (e.g., CT or MRI). Markers (e.g., a magnetic piece) may beused for intraoperative detection.

In some embodiments, installing the access device 100 may includepositioning the lumens in a burr hole above the cerebellum on the leftor right side. FIG. 6 depicts a diagram of a cross sectional view of anembodiment of an access device 100 implanted with the sampling andinfusion ports located adjacent, behind or over the cerebellum 208. Theinfusion and sampling catheter in the brain is connected to a container120 which is in turn connected to an implantable pump that is located inthe abdomen. In some embodiments, a small microinsertion device may beused to position the lumens of the device through a small opening ofless than one centimeter such that the lumens go through the burr holeopening. The inserted lumens may be flat or shaped like a tubing withtwo different pathways in it. The infusion pathway may infuse durallytowards the dura or towards the brainstem or medial or lateral. Theaspiration pathway may positioned in an opposing direction to theinfusion lumen, specifically such that the opening of the aspirationlumen is directed in an opposing direction to the opening of theinfusion lumen. In some embodiments, the openings may be facing the samedirection.

The pathway of placing the device may be determined by a CT scan or anMRI scan preoperatively. Scans may depict the subarachnoid cisterns andplacement of the catheter in the cerebellum. The targets could be any ofthe CSF subarachnoid cisterns including the cisterna magna,supracerebellar cisterns, CPA cistern or anterior to the brain stemcisterns. In some embodiments, a T-shaped separation 115 of the tubingas described herein may include one pathway directed towards anaspiration reservoir and one pathway directed towards an infusionsystem. In some embodiments, a stylet as described herein may be placedin the infusion lumen (or the aspiration lumen) when positioning thedevice in the subject. This same approach could be used to position thedevice over the sylvian fissure or interhemisphernic cistern.

Elements in common to both a supracerebellar device and a hemispheredesign include positioning the lumens through a small opening. Othercommon elements may include using preoperative imaging as a positioningguide and potentially using intra operative imaging as a positioningguide using either magnetic pieces in the device to see location andshape or using intraoperative MRI or intraoperative CT scan duringpositioning of the device. Common elements may include having a shape sothat it would be anchored to the skull outside the cranium, and/or astylet to guide passageway. For example, the container may includeexterior adhesive means for coupling the container to an exteriorsurface of the cranium.

In some embodiments, the aspiration lumen and the infusion lumen aredifferent lengths when positioned, during use, in the subject's brainsuch that a distal end of the aspiration lumen and a distal end of theinfusion lumen are positioned a distance away from one another. FIG. 7depicts a diagram of a cross sectional view of an embodiment of aportion of an intraventricular access device 100, specifically a side byside dual lumen design. The infusion and sampling ports 110 areimplanted in one of the lateral ventricles 200. The infusion port (110b) is connected to an implanted pump located near the abdomen.Positioning the distal ends of the aspiration and infusion lumens adistance away from one another may inhibit cross contamination offluids.

The aspiration and infusion lumens may have different physicalrelationships relative to one another. FIGS. 8A-C depict diagrams of across sectional view of several embodiments of a various dual lumencatheters 110 that may be used for the device described herein. In someembodiments, at least a portion of the infusion lumen is positioned inthe aspiration lumen or at least a portion of the aspiration lumen ispositioned in the infusion lumen (e.g., as depicted in FIGS. 1 and 8A).In some embodiments, the aspiration lumen and the infusion lumen mayinclude a single lumen divided into two different lumens with a wall ordivider (e.g., as depicted in FIG. 8B). In some embodiments, theaspiration lumen and the infusion lumen may include two different lumenspositioned adjacent one another (e.g., as depicted in FIGS. 5 and 8C).

In some embodiments, a distal end of the aspiration lumen comprises afirst opening and a distal end of the infusion lumen comprises a secondopening. The first opening and the second opening may be directed in asubstantially opposing directions (e.g., at least orthogonally relativeto one another) to inhibit cross contamination of fluids. The openingsmay be directed away from one another by bending (e.g., duringfabrication and/or implantation) at least a portion of at least one ofthe distal ends of the aspiration and/or infusion lumen.

In some embodiments, a distal end of the aspiration lumen and/or theinfusion lumen comprises at least one opening or a plurality ofopenings. In some embodiments, a distal end of the aspiration lumenand/or the infusion lumen comprises at least one opening which isinhibited from opening except when pressure is applied to the opening.FIG. 9 depicts a diagram of a cross sectional view of an embodiment of aportion of an intraventricular access device 100, specifically a side byside dual lumen design with multiple flow holes 170 in the infusioncatheter 110 b. The flow holes may be open or may each consist of small“slits” that open when drug is infused (when there is positive pressure)and close when drug is not infused. This may be accomplished using anumber of different methods. For example the opening may include a slitcut into a substantially resilient materials which flexes when underpressure but returns to an original shape after the pressure subsides(the original shape being a substantially closed slit in the lumen). Theopening may include a more traditional opening closed off with a hingedcover (e.g., the hinge may include a resilient material as describedherein since traditional mechanical hinges may be difficult tomanufacture at the current dimensions).

In some embodiments, at least a portion of the container is formed frommaterial that is penetrable by a needle and substantially reseals afterextraction of the needle. In some embodiments, specialized needles maybe employed that allow resealing and multiple penetrations whencerebrospinal fluid is aspirated. Specialized needles may includenon-coring needles. For example a small non-coring butterfly needle maybe used to (e.g., 23 or 25 gauge connected to a three-way tap) accessthe reservoir and collect a small amount of CSF.

The portion of the container may be on a proximal portion at least in arelation to the aspiration lumen such that the portion is facing awayfrom the subject and therefore accessible. At least a portion or all ofthe container may be positioned subcutaneously in the subject (e.g.,between a subject's skull and skin). The resealable portion of thecontainer may be exposed through the skin of the patient or bepositioned beneath the skin. The resealable portion of the container maybe formed from silicon. The reasealable portion may include an openingwith a recloseable cap or stopper. The resealable portion may bereplaceable after implantation.

Up to 25% of brain catheters fail due to clotting or tissues growinginto the catheter holes. Thus, there is a need for a new type ofcatheter to limit tissue adherence as well as the risk of infection.Fibrous adhesions may bind the intrabrain portion of the infusion systemto the proximate choroid plexus. Gentle rotation may free the catheterfrom the choroid plexus. If the catheter is stuck to the choroid plexusand is forcefully removed, there may be intraventricular hemorrhage.Thus, there exists a need to develop a catheter with an outer coatingthat also limits adherence and in-growth of tissue, particularly fromthe choroid plexus. In some embodiments, at least portions of the deviceare formed from and/or coated in biocompatible materials which inhibitcell adhesion. In some embodiments, biocompatible materials such asPebax, HIVE, LDPE, PTFE (polytetrafluoroethylene), ePTFE (expandedpolytetrafluoroethylene), and polyimide may be used to inhibit celladhesion. For example, as regards ePTFE independent experimental andclinical studies have demonstrated that the tight microstructure of theePTFE surface of GORE PRECLUDE® PDX Dura Substitute is effective atminimizing tissue attachment. With an average porosity of less than onemicron, the microstructure prevents penetration by fibroblasts and othermesenchymal cells and thus minimizes dense fibrous ingrowth.

In some embodiments, mechanical smoothing may be used on portions tolimit micro locations for adhesions and the shapes of the holes can bemade slit-like or very small via manufacturing techniques such as lasermicromachining.

In some embodiments, at least portions of the device are formed fromand/or coated in biocompatible materials comprising an antimicrobial.Antibacterial coatings composed of either silver or antibioticimpregnation similar to the catheters currently on the market. Portionsof the device may be impregnated with antibiotics (e.g., rifampicin andclindamycin).

Choice of materials may be important as regards manufacture of devicesdescribed herein. For example, granuloma associated with morphine spineinfusion has been of concern. Being careful of the molecule (morphineappears to be a major culprit), making sure the device materials in theinfusion system are produced using high quality products to avoidimpurities, and/or placing the catheter in areas of high CSF flowrelative the flow in the spinal areas, may result in the risk forgranulomas being minimized.

The system can either be modular or in one continuous system. Thecatheter is in one system or can be in two pieces from the container.The container may be either preassembled with a top or with the top thatcan be added separately. If the top is in place, a modified spinalneedle or another rigid type device is necessary for controlledplacement. If it is in two pieces a standard cannula can be in placethat is not sharp.

In some embodiments, during implantation general procedures of importmay include long tunneling, antibiotic cuffs at entry sites, usingfilters, avoiding flushing, maintaining sterile techniques, sometimesusing injected antibiotics and/or educating patients on self-care.

FIGS. 9-11 depicts a diagram of a top view of an embodiment of a portionof an implanted intraventricular access device detailing an implantationmethod. In some embodiments, insertion of devices described herein mayinclude inserting extraventricular drains at Kocher's point 190, to havethe catheter tip in the frontal horn of the lateral ventricle. Thecatheter may be inserted on the right side of the brain via a frontalincision 192. The burr hole 194 may be created using a ventriculostomyprocedure, sterile techniques, verification of catheter placement,tunneling 196 (including one or more incisions 198) and connections todrug pump. The catheter is designed to facilitate ease of use, accuracy,safety and durability of the procedure and the implant.

In some embodiments, a method includes aspirating and infusing at leasta portion of a subject's brain fluid. The method may include penetratingan upper portion of a container of a device using a needle. The methodmay include aspirating a first fluid from a first portion of a subject'sbrain fluid through an aspiration lumen coupled to the container andusing the needle. The method may include infusing a second fluid into asecond portion of a subject's brain fluid through an infusion lumencoupled to the container and the aspiration lumen. The method mayinclude inhibiting penetration of the infusion lumen by the needle.

In some embodiments, the method may include infusing the second fluidusing a pump coupled to the infusion lumen. The pump may be positionedexternally or internally (e.g., subcutaneously, in a body cavity, etc.)relative to the subject. The method may include positioning at least aportion of the infusion lumen coupled to a pump subcutaneously.

In some embodiments, the method may include positioning at least aportion of the aspiration and/or the infusion lumen in the subject'sbrain using a substantially inflexible stylet. The stylet may bepositioned in the aspiration lumen by running the stylet through thecontainer. FIGS. 8D-F depict a stylet 115 positioned in one or morelumens during installation of the device described herein. The stylet115 may be used to insert the device in a subject's brain fluid. Thestylet may be positioned in the aspiration and/or the infusion lumen.The stylet may be more than about 7 ems in length. The stylet maypenetrate at least ½ the length of the aspiration catheter within thebrain during use. If the stylet is positioned in both lumens, either twostylets may be used or one stylet with a split end may be used. Themethod may include observing at least a portion of the device duringimplantation using neuroimaging (e.g., MRI). Towards that end many ifnot all of the materials used to form the device may be compatible withcommon neuroimaging devices such as MRI.

In some embodiments, a stylet may be used to assist insertion of thedevice by positioning the stylet in the aspiration lumen before thereservoir or through the reservoir for aspiration. In some embodiments,a stylet may be used to assist insertion of the device by positioningthe stylet in the infusion lumen before connection to an implantable orexternal pump.

In some embodiments, the method may include inhibiting penetration ofthe infusion lumen by the needle using a barrier positioned between aproximal opening of the aspiration lumen and at least a portion of theinfusion lumen adjacent to and/or associated with the container. Thebarrier may inhibit cross contamination in general between the lumens.In some embodiments, the barrier may be formed from the same materialsas the container but may consist of a greater thickness (this maytactically alert a care giver inserting a needle that they areunknowingly inserting the needle to far into the container and close topenetrating the barrier. In some embodiments, the barrier may be formedfrom a different material than the container. The barrier may be formedfrom a substantially rigid, rigid, or inflexible material such as PTFEor a metal or metal composite.

In some embodiments, the method may include inhibiting at least oneopening at a distal end of the aspiration lumen and/or the infusionlumen from allowing fluids through the opening except when at leastpredetermined amount of pressure is applied to the opening in a firstdirection. The method may include inhibiting the opening from allowingfluids through the opening in a second direction even under pressure.

In this patent, certain U.S. patents, U.S. patent applications, andother materials (e.g., articles) have been incorporated by reference.The text of such U.S. patents, U.S. patent applications, and othermaterials is, however, only incorporated by reference to the extent thatno conflict exists between such text and the other statements anddrawings set forth herein. In the event of such conflict, then any suchconflicting text in such incorporated by reference U.S. patents, U.S.patent applications, and other materials is specifically notincorporated by reference in this patent.

Further modifications and alternative embodiments of various aspects ofthe invention will be apparent to those skilled in the art in view ofthis description. Accordingly, this description is to be construed asillustrative only and is for the purpose of teaching those skilled inthe art the general manner of carrying out the invention. It is to beunderstood that the forms of the invention shown and described hereinare to be taken as the presently preferred embodiments. Elements andmaterials may be substituted for those illustrated and described herein,parts and processes may be reversed, and certain features of theinvention may be utilized independently, all as would be apparent to oneskilled in the art after having the benefit of this description of theinvention. Changes may be made in the elements described herein withoutdeparting from the spirit and scope of the invention as described in thefollowing claims.

1. An intraventricular access device, comprising: a catheter includingan aspiration lumen and an infusion lumen, wherein a distal end of thecatheter is positionable, during use, in a subject's brain fluid; and acontainer coupled to a proximal end of the aspiration lumen, wherein theproximal end of the aspiration lumen is in fluid communication with thecontainer; wherein a proximal end of the infusion lumen is coupled,during use, to an external or implantable pump.
 2. The intraventricularaccess device of claim 1, wherein at least a portion of the infusionlumen is positioned in the aspiration lumen or at least a portion of theaspiration lumen is positioned in the infusion lumen.
 3. Theintraventricular access device of claim 1, wherein the aspiration lumenand the infusion lumen comprise two different lumens positioned adjacentand coupled to one another.
 4. The intraventricular access device ofclaim 1, wherein the aspiration lumen and the infusion lumen aredifferent lengths and have different tip locations when positioned,during use, in the subject's brain fluid such that a distal end of theaspiration lumen and a distal end of the infusion lumen are positioned adistance away from one another.
 5. The intraventricular access device ofclaim 1, wherein a distal end of the aspiration lumen comprises a firstopening and a distal end of the infusion lumen comprises a secondopening, and wherein the first opening and the second opening aredirected in a substantially opposing directions to inhibit crosscontamination of fluids.
 6. The intraventricular access device of claim1, wherein a distal end of the aspiration lumen and/or the infusionlumen comprises at least one opening which is inhibited from openingexcept when pressure is applied to the opening.
 7. The intraventricularaccess device of claim 1, wherein a distal end of the aspiration lumenand/or the infusion lumen comprises a plurality of openings which areinhibited from opening except when pressure is applied to the opening.8. The intraventricular access device of claim 1, wherein at least aportion of the container is formed from material that is penetrable by aneedle and substantially reseals after extraction of the needle.
 9. Theintraventricular access device of claim 1, wherein the containercomprises a barrier positioned between a proximal opening of theaspiration lumen and at least a portion of the infusion lumen adjacentto and/or associated with the container.
 10. The intraventricular accessdevice of claim 1, wherein the container comprises a barrier positionedbetween a proximal opening of the aspiration lumen and at least aportion of the infusion lumen adjacent to and/or associated with thecontainer, and wherein the barrier inhibits penetration of a surgicalinstrument and/or contamination of the infusion lumen.
 11. Theintraventricular access device of claim 1, wherein the containercomprises a barrier positioned between a proximal opening of theaspiration lumen and at least a portion of the infusion lumen adjacentto and/or associated with the container, and wherein the containercomprises a marker to indicate a position of the barrier and/or thecenter of the container to target aspiration.
 12. The intraventricularaccess device of claim 1, wherein at least portions of the device areformed from and/or coated in biocompatible materials which inhibit celladhesion and/or comprises an antimicrobial.
 13. A method of aspiratingand infusing into at least a portion of a subject's brain fluid,comprising: positioning a portion of a device in or adjacent to asubject's brain; penetrating an upper portion of a container of a deviceusing a needle; aspirating a first fluid from a first portion of thesubject's brain fluid through an aspiration lumen coupled to thecontainer and using the needle; infusing a second fluid into a secondportion of a subject's brain fluid through an infusion lumen coupled tothe container and the aspiration lumen; and infusing the second fluidusing a pump coupled to the infusion lumen, wherein the pump ispositioned externally or internally relative to the subject. 14.(canceled)
 15. The method of claim 13, further comprising implanting atleast a portion of the aspiration and/or the infusion lumen in thesubject's brain using a substantially inflexible stylet
 16. The methodof claim 13, further comprising observing at least a portion of thedevice during implantation using neuroimaging.
 17. The method of claim13, further comprising subcutaneously positioning at least a portion ofthe infusion lumen coupled to a pump.
 18. The method of claim 13,further comprising inhibiting penetration and/or contamination of theinfusion lumen using a barrier positioned between a proximal opening ofthe aspiration lumen and at least a portion of the infusion lumenadjacent to and/or associated with the container.
 19. The method ofclaim 13, further comprising inhibiting penetration of the infusionlumen by a sampling needle using a barrier positioned between a proximalopening of the aspiration lumen and at least a portion of the infusionlumen adjacent to and/or associated with the container.
 20. (canceled)21. (canceled)
 22. A method of aspirating and infusing into at least aportion of a subject's brain fluid, comprising: penetrating an upperportion of a container of a device using a needle; aspirating a firstfluid from a first portion of the subject's brain fluid through anaspiration lumen coupled to the container and using the needle; andinfusing a second fluid into a second portion of a subject's brain fluidthrough an infusion lumen coupled to the container and the aspirationlumen.